title: BML-111, a lipoxin receptor agonist, ameliorates 'two-hit'-induced acute pancreatitis-associated lung injury in mice by the upregulation of heme oxygenase-1.
abstract: The objective of this study is to investigate the effects of BML-111 on acute pancreatitis-associated lung injury (APALI) induced by cerulein with subsequent an LPS administration in mice and its possible mechanisms. One hundred and twenty-eight mice were randomly allocated to four groups, namely the APALI group, the BML-111 pretreatment group, the BM-111 control group, and the control group. The 'two-hit' mice APALI model was established by intraperitoneal injection of cerulein 7 times at hourly intervals and Escherichia coli lipopolysaccharide (LPS) once after the last dose of cerulein immediately. The samples were taken at 3, 6, 12, and 24 h after the last injection. Serum levels of amylase, TNF-a, IL-1β and IL-10, were determined. Histological score of the pancreas and lung, the wet/dry weight ratio, and heme oxygenase-1 (HO-1) expression in the lung were also evaluated. BML-111 pretreatment significantly reduced the serum levels of amylase, TNF-α, IL-1β, the wet/dry weight ratio of lung, and the pathology injury scores of pancreas and lung, and the serum levels of IL-10 were markedly increased. The severity of pancreatic and lung histology were also significantly improved by the administration of BML-111, and the expressions of HO-1 in lung tissues also increased in the BML-111 group compared with those in the APALI group. In conclusion, BML-111 exerts protective effects on APALI induced by cerulein and LPS. In addition to its anti-inflammatory effects, the beneficial effects may also be due to the upregulation of HO-1 expression in the lung tissues.
authors.affiliation: Department of General Surgery, Hepato-biliary-pancreatic institute, Lanzhou University Second Hospital , Lanzhou , P. R. China.
authors.forename: Ying Zhen
authors.initials: YZ
authors.lastname: Wang
authors.forename: You Cheng
authors.initials: YC
authors.lastname: Zhang
authors.forename: Jun Sheng
authors.initials: JS
authors.lastname: Cheng
authors.forename: Qian
authors.initials: Q
authors.lastname: Ni
authors.forename: Pei Jie
authors.initials: PJ
authors.lastname: Li
authors.forename: Shi Wen
authors.initials: SW
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Yu Long
authors.initials: YL
authors.lastname: Zhang
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002108:Ceruletide / Q000008:administration & dosage; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D044067:Receptors, Lipoxin / Q000819:agonists; D015854:Up-Regulation
chemical_list: C530770:5(S),6(R)-7-trihydroxyheptanoic acid, methyl ester; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006538:Heptanoic Acids; D008070:Lipopolysaccharides; D044067:Receptors, Lipoxin; D002108:Ceruletide; D051547:Heme Oxygenase-1; D000681:Amylases